Methicillin-resistant Staphylococcus aureus (MRSA) is a serious pathogen that causes patient mortality. Over 50% of infections around the world are caused by MRSA. MRSA has emerged as a community-associated pathogen (CA-MRSA), usually resulting in skin infections with abscess formation and cellulites in individuals who have not been hospitalized within the last year. Moreover, hospital-acquired infections of MRSA (HA-MRSA), relative to CA-MRSA, have been shown to be resistant to multiple antibiotics.
Two mechanisms of resistance of MRSA to the β-lactam antibiotics are inactivation by β-lactamase and the production of a penicillin binding protein PBP2a with decreased affinity for the antibiotics. The resistance PBP2a genotype of MRSA strains is encoded mecA gene which is transported on a mobile genetic element known as a staphylococcal cassette chromosome (SCC). The differences in susceptibility of HA-MRSA and CA-MRSA can be attributed to different SCCmec types (types IV and V for CA-MRSA and types I, II and III for HA-MRSA). These genes are associated with resistance to multiple drug classes, in addition to β-lactam antibiotics. CA-MRSA isolates are primarily resistant to β-lactam antibiotics (penicillins, cephalosporins, carbapenems) and macrolides and where initiation of antibiotic therapy may not be necessary in all patients with skin soft tissue infections caused by CA-MRSA.
Vancomycin has been the drug of choice despite a success rate of 35-57% and side effects including nosocomial pneumonia, skin and soft tissue infections, in addition to low bone penetration limit vancomycin's utility. Moreover, the increased use of vancomycin, especially in chronic patients has resulted in the emergence of MRSA with reduced susceptibility to glycopeptides.
The most effective anti-MRSA drug used today is daptomycin, a cyclic lipopeptide derived from the fermentation of Streptomyces roseosporus. Daptomycin is most useful for use in short duration and to treat persistent MRSA unaffected by other drug treatments such as vancomycin. Its mechanism of action involves binding to the bacterial cell membrane, causing depolarization of the membrane potential leading to inhibition of protein, DNA and RNA synthesis. Unfortunately, the FDA has reported some side effects for daptomycin, including an increase in blood creatine phosphokinase, rhabdomyolysis, skin exfoliation and skin ulcers.
Efforts have been made to decrease infection and colonization of MRSA in hospitals and other environments including the use of products that sterilize surfaces, including hand washes. Products containing 4% chlorhexidine gluconate (CHG) and 1% triclosan reduce the total bacterial count. The 4% CHG is more effective at reducing the total count than 1% triclosan; however, 1% triclosan has the ability to remove MRSA while 4% CHG cannot. Povidone-iodine used as an intranasal cream by the physicians and nurses working in the neonatal intensive care unit shows a 10% reduction in the isolation of MRSA pathogens.
Platanus occidentalis, the American Sycamore (fam. Platanaceae) has been known for its high safety profile in the treatment of a wide variety of conditions in traditional folk medicine. Species of Platanaceae have been used frequently for their antimicrobial and antiseptic properties. Native Americans used the American sycamore for cold and cough remedies, as well as dietary, dermatological, gynecological, respiratory, and gastrointestinal aids. The bark was used with honey locust to relieve hoarseness and sore throats as well as to treat skin eruptions, scabs and eczema, lung troubles, hemorrhages and tuberculosis. The mixture of the bark with the stem and twigs was used to treat knife and axe wounds. In addition, the bark has been used to treat colds, for purifying blood, for weight gain and as an analgesic. Finally, sycamore was also taken as cathartic, emetic and anti-diarrheal drug to treat dysentery.
Platanus occidentalis L. is a massive perennial tree up to 50 m in height, up to 4 m in diameter and usually found near lakes and streams. Several chemical investigations have shown the presence of triterpene secondary metabolites. This species is also reported to produce betulinic aldehyde, betulinic acid, platanic acid, β-sitosterol, and tiliroside as well as kaempferol 3-O-rhamnosides. Moreover, some polar and non-polar glycosides have been reported from members of the Platanaceae family.
Because of the increasing presence of MRSA-related infections and the lack of acceptable antibiotic therapy, new antibacterial compounds are needed.